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A candidate NAD+ transporter in an intracellular bacterial symbiont related to Chlamydiae

Nature volume 432, pages 622–625 (2004)Cite this article

Abstract

Bacteria living within eukaryotic cells can be essential for the survival or reproduction of the host1,2 but in other cases are among the most successful pathogens3,4. Environmental Chlamydiae, including strain UWE25, thrive as obligate intracellular symbionts within protozoa; are recently discovered relatives of major bacterial pathogens of humans; and also infect human cells4,5,6,7. Genome analysis of UWE25 predicted that this symbiont is unable to synthesize the universal electron carrier nicotinamide adenine dinucleotide (NAD+)7. Compensation of limited biosynthetic capacity in intracellular bacteria is usually achieved by import of primary metabolites8,9,10,11. Here, we report the identification of a candidate transporter protein from UWE25 that is highly specific for import of NAD+ when synthesized heterologously in Escherichia coli. The discovery of this candidate NAD+/ADP exchanger demonstrates that intact NAD+ molecules can be transported through cytoplasmic membranes. This protein acts together with a newly discovered nucleotide transporter and an ATP/ADP translocase12, and allows UWE25 to exploit its host cell by means of a sophisticated metabolic parasitism.

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Figure 1: Effect of metabolites on ADP or NAD+ uptake by NTT4 and substrate saturation analysis.
Figure 2: Back exchange properties of NTT4.
Figure 3: Transcriptional analysis of ntt1 (top) ntt2 (middle) and ntt4 (bottom) of strain UWE25 during multiplication within Acanthamoeba.
Figure 4: Model for metabolic interactions between UWE25 and its amoeba host.

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Acknowledgements

Work in the laboratory of H.E.N. was supported by the DFG and the local research centre ‘Neue Wirkstoffe’, funded by the Federal State Rheinland-Pfalz. Work in the laboratory of M.W. was supported by the Austrian Science Fund (FWF) and by the Austrian Federal Ministry for Education, Science and Culture in the context of the GEN-AU project ‘Environmental Chlamydia Proteomics’.

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Authors and Affiliations

  1. Pflanzenphysiologie, Universität Kaiserslautern, D-67653, Kaiserslautern, Germany

    Ilka Haferkamp, Nicole Linka, Claude Urbany & H. Ekkehard Neuhaus

  2. Abteilung Mikrobielle Ökologie, Institut für Ökologie und Naturschutz, Universität Wien, 1090, Wien, Austria

    Stephan Schmitz-Esser, Astrid Collingro, Michael Wagner & Matthias Horn

Authors
  1. Ilka Haferkamp
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  2. Stephan Schmitz-Esser
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  3. Nicole Linka
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  4. Claude Urbany
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  7. Matthias Horn
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  8. H. Ekkehard Neuhaus
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Corresponding author

Correspondence to H. Ekkehard Neuhaus.

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Supplementary information

Supplementary Data

This file contains Supplementary Table 1 (proteins with homology to the NAD+/ADP transporter NTT4 of UWE25 in the public databases EMBL/GenBank/DDBJ), Supplementary Figure 1 (amino-acid sequence alignment of various NTT-type proteins from intracellular bacteria and plants), Supplementary Figure 2 (Nucleotide transport catalyzed by NTT2 and NTT4), and Supplementary Figure 3 (Phylogenetic relationships of nucleotide transport proteins). (DOC 113 kb)

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Haferkamp, I., Schmitz-Esser, S., Linka, N. et al. A candidate NAD+ transporter in an intracellular bacterial symbiont related to Chlamydiae. Nature 432, 622–625 (2004). https://doi.org/10.1038/nature03131

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